Genes and environment in type 1 diabetes : a multi-species approach

Professor Lucy Davison has been awarded a MRC Clinician Scientist Fellowship to work on "Genes and Environment in Diabetes Mellitus: a multi-species approach".

Type 1 diabetes mellitus (T1D) arises as the result of many different genetic and environmental factors, most of which are not fully understood. In affected patients, the insulin-producing beta cells in the pancreas are destroyed. As a result, patients are dependent on lifelong daily insulin injections. T1D affects more than 400,000 people in the UK including up to 30,000 children. Diabetes mellitus is also commonly diagnosed in veterinary medicine, affecting 1 in 300 dogs, with certain breeds being genetically pre-disposed. This 5-year project aims to understand the environmental influences involved in the development of T1D, and how these environmental factors interact with genetic risk.

The incidence of T1D has been rising year on year since the 1950s, co-inciding with more frequent use of antibiotics for childhood infections. One theory is that antibiotics disrupt the balance of micro-organisms, such as bacteria, in the gut. Together, these micro-organisms are known as the microbiome. The microbiome plays an important role in the development of the immune system, and a healthy microbiome is thought to be involved in protecting against the development of T1D. Studies of the microbiome in children with T1D demonstrate differences in the type, frequency and diversity of micro-organisms compared to children without T1D. It has also been shown that some of the chemicals (metabolites) made by the bacteria in the microbiome are important for healthy immune system function, with certain metabolites having a protective effect in T1D.

This study will examine the relationship between DNA variations, the microbiome and risk of diabetes across multiple species, including dogs and humans. The microbiome will be studied by looking at the genetic material from micro-organisms in the faeces of pre-diabetic, diabetic and non-diabetic individuals. We will also use ‘metabolomics’ technology to determine whether any markers in the blood can provide useful information about the health of the microbiome. In addition, the impact of changes in the microbiome on the immune system and the development of T1D will be explored using new technology called single-cell transcriptomics.

In the canine species, this project will use the VetCompass database to investigate whether any relationship between antibiotic use and diabetes diagnosis can be identified in dogs. Investigation of microbiome of diabetic dogs will complement ongoing work studying the genetics of canine diabetes (caninediabetesgenetics.org).

In future, we hope that the data generated in this project will help us to prevent diabetes in genetically-susceptible individuals by altering the microbiome.